NSF-BSF: Synchronous electro-optical DNA detection using low-noise dielectric nanopores on sapphire

NSF-BSF：使用蓝宝石上的低噪声介电纳米孔进行同步电光 DNA 检测

• 批准号: 2020464
• 负责人: Chao Wang
• 金额: $ 36万
• 依托单位: Arizona State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2020464&HistoricalAwards=false
• 关键词: NSF; BSF; Synchronous; electro; optical

Nanopore DNA sensing is an emerging technology, and has recently been developed to detect both the DNA primary sequence and epi-genetic information (such as methylation), which is crucial to both fundamental biology and precision medicine.. However, high-speed and accurate DNA methylation detection in nanopores still lags behind. This is attributed to an insufficient signal-to-noise ratio (SNR) resulting from the inherent large electrical capacitive noise from the conductive silicon (Si) and also the complex DNA dynamic interaction with nanopore surface. This project proposes a multidisciplinary research plan to address the fundamental challenges in high-speed and low-noise biomolecular sensing in a solid-state nanopore device. The new design combines electrical and optical sensing on a single sensor platform to improve the sensing accuracy. It utilizes crystalline sapphire as an insulating substrate and integrates large-bandgap titanium oxide thin film as the sensing element to minimize both the electronic and optical noise. The demonstration of DNA methylation detection will prove the feasibility of our TiO2/sapphire nanopore sensors in detecting complex molecular structures that will have broad impact on molecular marker detection and molecule-molecule interactions. The educational objectives are to promote electronic nanosensors related engineering education to undergraduate and graduate students, and to better prepare them as future innovators to transform nanobiotechnologies. The outreach objectives are to promote public awareness of the importance of nanosensors in health care and to attract the participation of K-12 students and underrepresented individuals in STEM careers.This research is to fill the knowledge gap in nanopore sensing research by creating a significantly improved nanopore sensor platform that integrates low-optical background titanium oxide membranes on low-capacitance and hence low-electrical-noise sapphire. The research team will fabricate small and thin TiO2 membranes on sapphire, establish high-throughput manufacturing methods for both membrane formation and nanopore drilling, perform single-molecule DNA translocation, study the DNA-nanopore interaction, and analyze the data for methylation detection. The proposed sensor platform has a number of key features to support the development of a wide variety of emerging biomolecular diagnostic technologies. First, the creation of ultrasmall (10 μm) dielectric membranes on insulating sapphire eliminates substrate conductance, and drastically minimizes the chip capacitance to a few picoFarads even for high-dielectric-constant and ultrathin (5 nm) TiO2 devices, thus significantly reducing the background high-frequency electrical noise and markedly improving high-bandwidth sensing. Further, both membrane formation and nanopore drilling will be achieved by high-throughput manufacturing methods, i.e. wafer-scale and batch-processing compatible sapphire etching and direct laser drilling, thus enabling low-cost and repeatable production. The scalably manufactured, low-noise, high-sensitivity nanopores will facilitate high-resolution gene identification and quantitation of their methylation status in a single measurement and at a greatly reduced cost.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

纳米孔DNA传感是一项新兴技术，最近开发用于检测DNA一级序列和表观遗传信息（例如甲基化），这对基础生物学和精准医学至关重要。然而，在纳米孔中的高速和准确的DNA甲基化检测仍然落后。这归因于由来自导电硅（Si）的固有大电容噪声以及与纳米孔表面的复杂DNA动态相互作用引起的不足的信噪比（SNR）。 该项目提出了一个多学科的研究计划，以解决固态纳米孔设备中高速和低噪声生物分子传感的基本挑战。新设计在单个传感器平台上结合了电学和光学传感，以提高传感精度。它利用晶体蓝宝石作为绝缘衬底，并集成大带隙氧化钛薄膜作为传感元件，以最大限度地减少电子和光学噪声。DNA甲基化检测的演示将证明我们的TiO 2/蓝宝石纳米孔传感器在检测复杂分子结构方面的可行性，这将对分子标记检测和分子-分子相互作用产生广泛影响。教育目标是促进电子纳米传感器相关的工程教育本科生和研究生，并更好地准备他们作为未来的创新者转变nanobiotechnologies。该项目旨在提高公众对纳米传感器在医疗保健领域的重要性的认识，吸引K-12学生和STEM职业中代表性不足的个人的参与。该研究旨在通过创建一个显着改进的纳米孔传感器平台来填补纳米孔传感研究的知识空白，该平台将低光学背景的氧化钛膜集成在低电容和低电噪声的蓝宝石上。研究团队将在蓝宝石上制造小而薄的TiO 2膜，建立膜形成和纳米孔钻孔的高通量制造方法，进行单分子DNA易位，研究DNA-纳米孔相互作用，并分析甲基化检测数据。拟议的传感器平台具有许多关键功能，以支持各种新兴生物分子诊断技术的发展。首先，在绝缘蓝宝石上制作超小（10 μm）介电薄膜消除了衬底电导，并将芯片电容大幅降至几皮法，即使对于高介电常数和纳米（5 nm）TiO 2器件也是如此，从而显著降低了背景高频电噪声，并显著改善了高带宽传感。此外，膜形成和纳米孔钻孔都将通过高通量制造方法实现，即晶圆级和批量加工兼容的蓝宝石蚀刻和直接激光钻孔，从而实现低成本和可重复的生产。可规模化制造的低噪音、高灵敏度纳米孔将有助于在一次测量中以大大降低的成本实现高分辨率基因识别和甲基化状态定量。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。

项目成果

Picomolar-Level Sensing of Cannabidiol by Metal Nanoparticles Functionalized with Chemically Induced Dimerization Binders

通过化学诱导二聚化粘合剂功能化的金属纳米颗粒对大麻二酚进行皮摩尔水平传感

• DOI: 10.1021/acssensors.3c01758
• 发表时间: 2023
• 期刊: ACS Sensors
• 影响因子: 8.9
• 作者: Ikbal, M. D.;Kang, Shoukai;Chen, Xiahui;Gu, Liangcai;Wang, Chao
• 通讯作者: Wang, Chao

Sapphire-supported nanopores for low-noise DNA sensing

用于低噪声 DNA 传感的蓝宝石支撑纳米孔

• DOI: 10.1016/j.bios.2020.112829
• 发表时间: 2021
• 期刊: Biosensors and Bioelectronics
• 影响因子: 12.6
• 作者: Xia, Pengkun;Zuo, Jiawei;Paudel, Pravin;Choi, Shinhyuk;Chen, Xiahui;Rahman Laskar, Md Ashiqur;Bai, Jing;Song, Weisi;Im, JongOne;Wang, Chao
• 通讯作者: Wang, Chao